Mindfulness Engaged Neurostimulation for Depression

Phase 2

Recruiting

• Conditions: Treatment Resistant Depression; Major Depressive Disorder; Depression; Depressive Disorder
• Interventions: Combination Product: Medi-TBS

• Registration Number: NCT06399406
• Lead Sponsor: University of California, San Diego

Brief Summary

Repetitive Transcranial Magnetic stimulation (rTMS) is an FDA-approved therapy for treatment resistant depression (TRD) that involves brief magnetic stimulation pulses on the dorsolateral prefrontal cortex (DLPFC) brain region. But studies of rTMS alone show remission rates of \~30%. Additionally, rTMS has not been shown to improve cognitive functioning that may be an independent factor predicting treatment success. This study will develop a novel multimodal treatment, which combines intermittent theta burst stimulation (iTBS) - a type of rTMS with digital mindfulness training to engage brain plasticity, enhance cognition and alleviate depression symptoms in individuals with TRD.

Detailed Description

This study aims to develop a novel multimodal treatment for treatment resistant depression (TRD), which combines intermittent theta burst stimulation (iTBS), a type of FDA-approved rTMS protocol, with digital mindfulness training. We propose that this multimodal treatment will suppress posterior Default Mode Network (pDMN) brain activity as measured with electroencephalography (primary outcome and neural target), as well as enhance cognition and alleviate depression symptoms in patients with TRD. The study will determine the optimal dose required for neural target engagement by the multimodal iTBS + digital mindfulness training relative to an active control training combined with iTBS.

Study Timeline

• Study First Submitted: 2024-04-30
• Study First Submitted QC: 2024-04-30
• Study First Posted: 2024-05-03
• Study Start: 2024-05-15
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-20
• Last Update Posted: 2024-06-24
• Primary Completion: 2026-04-30
• Study Completion: 2026-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• Diagnosis of major depressive episode (MDE, in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5), in the context of unipolar major depressive disorder.
• At least one failed antidepressant medication trial at level 3 in the Antidepressant Treatment History Form: Short Form (ATHF-SF) classification.
• Montgomery-Åsberg Depression Rating Scale (MADRS) Score >19 (moderate - severe depression).
• No increase or initiation of new antidepressant therapy in the four weeks prior to screening.
• Demonstrated capacity to give informed consent.

Exclusion Criteria

• Inability to provide informed consent.
• Medically unstable patients.
• Concomitant neurological disorder or a history of a seizure disorder.
• Exhibiting current suicidal behavior rating on the Columbia Suicide Severity Rating Scale (C-SSRS)
• Patients who are pregnant or breastfeeding.
• Any psychotic disorder or current active psychotic symptoms.
• Patients who have intracranial implants, other medical device or condition deemed unsafe for TMS.
• Contraindication to MRI scanning.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Medi3-TBS	Medi-TBS	This arm will receive a multimodal treatment with a digital mindfulness training focused on intermittent deep breathing for up to 10 min session dose for up to 20 sessions combined with neuro-navigated iTBS type of rTMS (for 20 treatments over 4 weeks) targeting the left dorsolateral prefrontal cortex (DLPFC) brain region.
Medi1-TBS	Medi-TBS	This arm will receive a multimodal treatment with a digital mindfulness training focused on attention to breathing for up to 10 min session dose for up to 20 sessions combined with neuro-navigated iTBS type of rTMS (for 20 treatments over 4 weeks) targeting the left dorsolateral prefrontal cortex (DLPFC) brain region.
Medi2-TBS	Medi-TBS	This arm will receive a multimodal treatment with a digital mindfulness training focused on attention to breathing for up to 20 min session dose for up to 20 sessions combined with neuro-navigated iTBS type of rTMS (for 20 treatments over 4 weeks) targeting the left dorsolateral prefrontal cortex (DLPFC) brain region.

Primary Outcome Measures

Name	Time	Method
Change in EEG source localized pDMN alpha activity	4 weeks	EEG alpha band (8-12 Hz) activity source-localized to the posterior Default Mode Network (pDMN) brain region extracted on distracted trials of the Breath Attention Assessment of Mindfulness task serves as the primary neural target.

Secondary Outcome Measures

Name	Time	Method
Change in Selective Attention	4 weeks	Processing speed of response to target stimuli on a standard continuous performance task that measures the ability to selectively attend and promptly respond to a goal-relevant target stimulus serves as the secondary cognitive target.
Change in Flanker Inhibition	4 weeks	Efficiency of inhibiting visuo-spatially flanking distractors to target stimuli in the Flanker task serves as the secondary cognitive target.
Change in Montgomery Åsberg Depression Rating Scale Scores (MADRS)	8 weeks	The MADRS will be used to evaluate % depressive symptom response defined as 50% change in the MADRS score from baseline as well as remission defined as MADRS score \<7 at post-intervention. Scale range: 0-54, higher score is worse depression.

Trial Locations

Locations (1)

University of California San Diego; 🇺🇸 La Jolla, California, United States